QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 15, Issue 10, 4609-4621, October 2004

This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: E04-03-0194v1 15/10/4609    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tedrick, K. Articles by Eitzen, G. Search for Related Content PubMed PubMed Citation Articles by Tedrick, K. Articles by Eitzen, G.

Enhanced Membrane Fusion in Sterol-enriched Vacuoles Bypasses the Vrp1p Requirement

Kelly Tedrick ^*, Tim Trischuk , Richard Lehner ^* , and Gary Eitzen ^* 

^* Department of Cell Biology, University of Alberta, Edmonton, Alberta, T6G 2H7 Canada; CIHR Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, T6G 2H7 Canada

Submitted March 9, 2004; Accepted July 1, 2004
Monitoring Editor: David Drubin

Organization of lipids into membrane microdomains is a vital mechanism of protein processing. Here we show that overexpression of ERG6, a gene involved in ergosterol synthesis, elevates sterol levels 1.5-fold on the vacuole membrane and enhances their homotypic fusion. The mechanism of sterol-enhanced fusion is not via more efficient sorting, but instead promotes increased kinetics of fusion subreactions. We initially isolated ERG6 as a suppressor of a vrp1 growth defect selective for vacuole function. VRP1 encodes verprolin, an actin-binding protein that colocalizes to vacuoles. The vrp1 mutant has fragmented vacuoles in vivo and isolated vacuoles do not fuse in vitro, indicative of a Vrp1p requirement for membrane fusion. ERG6 overexpression rescues vrp1 vacuole fusion in a cytosol-dependent manner. Cytosol prepared from the vrp1 strain remains active; therefore, cytosol is not resupplying Vrp1p. Las17p (Vrp1p functional partner) antibodies, which inhibit wild-type vacuole fusion, do not inhibit the fusion of vacuoles from the vrp1-ERG6 overexpression strain. Vacuole-associated actin turnover is decreased in the vrp1 strain, but recovered by ERG6 overexpression linking sterol enrichment to actin remodeling. Therefore, the Vrp1p/Las17p requirement for membrane fusion is bypassed by increased sterols, which promotes actin remodeling as part the membrane fusion mechanism.

The online version of this article contains supplemental material accessible through http://www.molbiolcell.org.

Corresponding author. E-mail address: gary.eitzen{at}ualberta.ca. Website: www.ualberta.ca/CELLBIOLOGY/eitzen.html.

This article has been cited by other articles:

				S. Isgandarova, L. Jones, D. Forsberg, A. Loncar, J. Dawson, K. Tedrick, and G. Eitzen Stimulation of Actin Polymerization by Vacuoles via Cdc42p-dependent Signaling J. Biol. Chem., October 19, 2007; 282(42): 30466 - 30475. [Abstract] [Full Text] [PDF]

				M. Holtta-Vuori, F. Alpy, K. Tanhuanpaa, E. Jokitalo, A.-L. Mutka, and E. Ikonen MLN64 Is Involved in Actin-mediated Dynamics of Late Endocytic Organelles Mol. Biol. Cell, August 1, 2005; 16(8): 3873 - 3886. [Abstract] [Full Text] [PDF]